Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 4-(1-(2-Ethyl-5-formyl-4-methylbenzoyl)piperidin-4-yl)benzonitrile

Temperature

25 °C

To a round-bottom flask was added a solution of 2-ethyl-5-formyl-4-methylbenzoic acid (compound 211.4, 450 mg, 2.34 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL). DIEA (907 mg, 7.02 mmol, 3.00 equiv) and HBTU (1.30 g, 3.43 mmol, 1.50 equiv) were added to the reaction mixture. The resulting solution was stirred for 30 min at 25° C. A solution of 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.5, 624 mg, 2.80 mmol, 1.20 equiv) in DIEA (2 mL) was added dropwise. The resulting solution was stirred for 30 min at 25° C., then quenched with 20 mL of water. The aqueous phase was extracted with 3×30 mL of ethyl acetate. The combined organic layers were washed with 1×50 mL of brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (5:1) as eluent to furnish 720 mg (85%) of the title compound as a yellow solid.

1. stirringThe resulting solution was stirred for 30 min at 25° C.
2. customquenched with 20 mL of water
3. extractionThe aqueous phase was extracted with 3×30 mL of ethyl acetate
4. washThe combined organic layers were washed with 1×50 mL of brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe residue was purified

ORD record

ord-daf62af2d4d94d60a35d4b873ae4b02b

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2